This phase II trial studies how well sorafenib tosylate works in treating younger patients with relapsed or refractory rhabdomyosarcoma, Wilms tumor, liver cancer, or thyroid cancer. Sorafenib tosylate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

A Phase II Study of the Raf Kinase and Receptor Tyrosine Kinase Inhibitor Sorafenib in Children and Young Adults With Relapsed/Refractory Rhabdomyosarcoma, Wilms Tumor, Hepatocellular Carcinoma, and Papillary Thyroid Carcinoma

Response rates will be calculated as the number of evaluable patients who are responders. Response Evaluation Criteria In Solid Tumors (RECIST) criteria: Complete Response (CR): Disappearance of all target lesions, Partial Response (PR): At least a 30% decrease in the sum of the LD of target lesions, taking as reference the baseline sum LD, Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started and Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

Secondary Outcome Measures:

Progression-free Survival According to RECIST Version 1.1 [ Time Frame: From date of enrollment to the date of disease progression, date of death, date of removal of all tumor by surgery or last patient contact, whichever occurs first, assessed up to 5 years ] [ Designated as safety issue: No ]

Progression-free interval (PFI) will be calculated as the date of enrollment until the end PFI date, where that date is calculated as the date of disease progression, date of death, date of removal of all tumors by surgery or last patient contact, whichever occurs first.

Toxicity as Assessed by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Pharmacokinetic (PK) Parameters of Sorafenib Tosylate [ Time Frame: At baseline, up to 12 hours and on day 15 of course 1, and prior to odd courses ] [ Designated as safety issue: No ]

The PK parameters will be summarized with simple summary statistics, including means, medians, ranges, and standard deviations (if numbers and distribution permit).

Change in VEGF and VEGFR-2 [ Time Frame: From baseline to day 15 of course 1 ] [ Designated as safety issue: No ]

Descriptive statistics including mean, median, standard deviation, and range will be calculated for baseline and steady state VEGF and VEGFR-2. Changes from baseline to steady state on treatment with sorafenib will be evaluated using non-parametric paired tests if there is evidence of intra-patient correlation as assessed by Spearman's rank correlation.

Presence of BRAF Mutation or RET/PTC Rearrangement [ Time Frame: At baseline ] [ Designated as safety issue: No ]

Descriptive statistics including mean, median, standard deviation, and range will be calculated for baseline for patients with PTC, TG and TG antibody, and presence of BRAF mutation or RET/PTC rearrangement.

Patients with relapsed or refractory rhabdomyosarcoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

Other Names:

BAY 43-9006

BAY 43-9006 Tosylate Salt

BAY 54-9085

Nexavar

SFN

Other: pharmacological study

Optional correlative studies

Other Name: pharmacological studies

Other: laboratory biomarker analysis

Optional correlative studies

Experimental: Group 2 Relapsed/Refractory Wilms tumor

Patients with relapsed or refractory Wilms tumor receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

Other Names:

BAY 43-9006

BAY 43-9006 Tosylate Salt

BAY 54-9085

Nexavar

SFN

Other: pharmacological study

Optional correlative studies

Other Name: pharmacological studies

Other: laboratory biomarker analysis

Optional correlative studies

Experimental: Group 3 Relapsed/Refractory hepatocellular carcinoma

Patients with relapsed or refractory hepatocellular carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Given PO dosage 200 mg/m2/dose (max dose:400 mg/dose) given every 12 hours on days 1-28

Other Names:

BAY 43-9006

BAY 43-9006 Tosylate Salt

BAY 54-9085

Nexavar

SFN

Other: pharmacological study

Optional correlative studies

Other Name: pharmacological studies

Other: laboratory biomarker analysis

Optional correlative studies

Experimental: Group 4 Papillary thyroid carcinoma

Patients with relapsed or refractory papillary thyroid carcinoma receive sorafenib tosylate PO BID on days 1-28. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

I. To further define and describe the toxicities of sorafenib administered on an oral, twice-daily continuous schedule.

II. To further characterize the pharmacokinetics of sorafenib in children with refractory cancer.

III. To estimate the progression-free survival on sorafenib for rhabdomyosarcoma, Wilms tumor, and hepatocellular carcinoma and compare to a group of patients enrolled on selected closed Phase II studies of Children Oncology Group (COG).

Patients must have radiographically measurable disease; measurable disease is defined as the presence of at least one lesion on magnetic resonance imaging (MRI) or computed tomography (CT) scan that can be accurately measured with the longest diameter a minimum of 10 mm in at least one dimension (CT scan slice thickness no greater than 5 mm)

Patients with HCC must be relapsed or refractory to conventional chemotherapy

Patients with PTC must be refractory to radioactive iodine (RAI)

Patient's current disease state must be one for which there is no known curative therapy or therapy proven to prolong survival with an acceptable quality of life

Patients with known metastasis to the brain will be excluded from trial participation unless treated surgically or with radiotherapy and stable with no recurrent lesions for at least 3 months

Rhabdomyosarcoma and Wilms strata: patients must be ≥ 24 months and ≤ 30 years of age at study enrollment

Hepatocellular carcinoma (HCC): patients must be ≥ 24 months and < 18 years of age at study enrollment

Papillary thyroid carcinoma (PTC): patients must be ≥ 24 months and ≤ 21 years of age at study enrollment

Patients must have a Lansky or Karnofsky performance status score of ≥ 50%, corresponding to ECOG categories 0, 1, or 2

Use Karnofsky for patients > 16 years of age and Lansky for patients ≤ 16 years of age

Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

Peripheral absolute neutrophil count (ANC) ≥ 1,000/μL

Platelet count ≥ 75,000/μL (transfusion independent, defined as not receiving platelet transfusions within a 7-day period prior to enrollment)

Hemoglobin 8.0 g/dL (may receive red blood cell[RBC] transfusions)

Creatinine clearance or radioisotope glomerular filtration rate(GFR) 70 mL/min OR a serum creatinine based on age/gender as follows:

0.8 mg/dL (2 to < 6 years of age)

1.0 mg/dL (6 to < 10 years of age)

1.2 mg/dL (10 to < 13 years of age)

1.5 mg/dL (male) or 1.4 mg/dL (female) (13 to < 16 years of age)

1.7 mg/dL (male) or 1.4 mg/dL (female) (≥ 16 years of age)

Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age

SGPT (ALT) ≤ 135 U/L (for the purpose of this study, the ULN for SGPT is 45 U/L)

PT, PTT, and INR < 1.5 times ULN

Normal serum lipase and amylase (per institutional normal values)

No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% if there is clinical indication for determination

A blood pressure (BP) ≤ the 95^th percentile for age, height, and gender; and not receiving medication for treatment of hypertension

Patients who are pregnant or breast-feeding are not eligible

Negative pregnancy tests must be obtained in girls who are post-menarchal

Males or females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method beginning at the signing of the informed consent until at least 30 days after the last dose of the study drug

Patients with clinical symptoms of hepatic encephalopathy or ascites are not eligible

Patients who have an uncontrolled infection are not eligible

Patients with evidence of bleeding diathesis are not eligible

Patients with known Gilbert syndrome are not eligible

Patients who, in the opinion of the investigator, may not be able to comply with the safety-monitoring requirements of the study are not eligible

Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study

Patients with solid tumors must not have received myelosuppressive chemotherapy within 3 weeks of enrollment onto this study (6 weeks if prior nitrosourea)

At least 7 days must have elapsed since the completion of therapy with a growth factor (at least 14 days must have elapsed after receiving pegfilgrastim)

At least 7 days must have elapsed since completion of therapy with a biologic agent;

For agents that have known adverse events occurring beyond 7 days after administration, this period prior to enrollment must be extended beyond the time during which adverse events are known to occur

At least 3 half-lives must have elapsed since prior therapy that included a monoclonal antibody

At least 2 weeks must have elapsed since local palliative radiotherapy (XRT) (small port); ≥ 3 months must have elapsed if prior craniospinal XRT was received, if ≥ 50% of the pelvis was irradiated, or if TBI was received; ≥ 6 weeks must have elapsed if other substantial bone marrow irradiation was given

No evidence of active graft-vs-host disease and ≥ 2 months must have elapsed since transplant (stem cell transplant or rescue without total-body irradiation)

Patients requiring corticosteroids that have not been on a stable or decreasing dose of corticosteroid for 7 days prior to enrollment are not eligible

Patients who are currently receiving another investigational drug are not eligible

Patients who are currently receiving other anti-cancer agents are not eligible

Patients who are receiving cyclosporine, tacrolimus or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post transplant are not eligible for this trial

Patients who take cytochrome P450 enzyme-inducing anti-epileptic drugs (phenytoin, carbamazepine, or phenobarbital), rifampin, grapefruit juice, or St. Johns wort will not be eligible for the trial

Patients who have received prior treatment with sorafenib are not eligible

Patients must not be on therapeutic anti-coagulation;

Prophylactic anticoagulation (i.e., low-dose warfarin) of venous or arterial devices is allowed provided that the requirements for prothrombin time(PT), partial thromboplastin time(PTT), and international normalized ratio(INR) are met

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01502410